Complexity is a hallmark of any biological system. In my K25 award period I will focus on applying Systems Science approaches to cancer biology in the context of complex systems, and transform myself into a Systems Cancer Biologist. As a System Scientist with two decades of experience, it was required of me to learn diverse fields quickly enough to collaborate with specialists in such dissimilar fields as astrodynamics, demographics, economics, engineering, health, hydrology, physics, and water chemistry. Interdisciplinary research requires 'learning the language' - i.e., to converse with disciplinary specialists to jointly define problems, understanding and, search for solutions. With an experiential learning approach with guidance from my mentors and collaborator, during my K25 period, I will develop specific 'small' research projects as a vehicle for learning about important cancer problems. Lab rotations in biology, imaging, pharmacology, etc., supplements knowledge, and in appreciating data collection, methodology and protocols, needed for model validation, analysis verification - essentially in silico approach, that leads to in vitro. The in vivo experiments will be in the longer term. With my quantitative and qualitative research background, I will focus on inter- and intra-cell signaling pathways, in particular JAK-STAT and Ras-Raf-MEK-ERK, and, on transcriptional and post-transcriptional gene expression networks. Understanding cross-talk and regulatory gene network behavior, requires defining problems using goal seeking, coordination, bounded autonomy, resilience and robustness paradigms, and the application of systems science approaches of multilevel and hierarchical systems theory, coordination and control. Cell functions such as apoptosis, angiogenesis, tissue invasion, proliferation, metastasis and differentiation, important in cancer biology will provide motivation for this research. Over the next two decades I will work to be a leader and co-leader with cancer biologists and, collaborate with physicians- essentially bench-to-bed. As an educator, I will create a Systems Cancer Biology course to train a new cadre of students in both engineering and cancer biology. In the longer term I will co-develop a curriculum to replicate my experience in creating more Systems Cancer Biologists.